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MMWR 37(45);693-694,699-704

Publication date: 11/18/1988

Table of Contents

Article

Simian immunodeficiency virus (SIV) belongs to the family Retroviridae
(subfamily Lentivirinae) and is closely related to human
immunodeficiency virus types 1 and 2 (HIV-1 and HIV-2), the etiologic
agents of acquired immunodeficiency syndrome (AIDS). Although no
reports of infection in humans have been documented, the expanding use
of SIV as a model of HIV infection has raised concern about the
potential risk of SIV transmission to humans. Therefore, a working
group was established by CDC and the National Institutes of Health
(NIH) to formulate specific guidelines intended to minimize the risk of
SIV transmission to humans.

BACKGROUND

Originally reported in 1985, the first isolate from a rhesus macaque
was called simian T-lymphotropic virus III (STLV-III) (1). Viral
isolates have since been obtained from several species of nonhuman
primates including African green monkeys (2), sooty mangabeys (3),
pig-tailed macaques (4), and stump-tailed macaques (5). Limited studies
of wild-caught African green monkeys from Central Africa indicate a
seroprevalence of approximately 30%-50%, apparently without associated
immunodeficiency disease. The seroprevalence of SIV among rhesus
monkeys in captive colonies (whether from natural infections or
interspecies transmission) appears to be low (i.e., 0-1%) (6). In
contrast, captive sooty mangabeys may have seroprevalence rates as high
as 80% (H. McClure, personal communication). The prevalence of SIV
infection among many other nonhuman primate species is unknown.
In rhesus monkeys and other susceptible nonhuman primate
species (e.g. pig-tailed macaque, crab-eating macaque), SIV
infection leads to a chronic wasting disease syndrome with
depletion of CD4 (T4) lymphocytes and lymphadenopathy. The
clinical course of this infection in monkeys, like that of AIDS
in humans, is complicated by various opportunistic infections
(7). SIV also causes a primary encephalopathy with many of the
features of HIV-associated encephalopathy (8). Therefore, SIV
infection is an important animal model of AIDS. SIV proteins,
especially the viral core proteins (i.e., p24, capsid protein),
are antigenically related to HIV-I proteins (9). Some SIV
isolates, however, are antigenically more related to HIV-2 than
to HIV-I by cross-reactivity of viral capsid and envelope
proteins. SIV isolates that have been molecularly cloned share
approxi-mately 75% of their genomic sequences with HIV-II and
approximately 30% with NIV-I (10). SIV isolates are clearly
distinct from Type D primate retrovirus (i.e., simian retrovirus
1)that also causes a form of chronic wasting immunodeficiency
disease in several primate species (ll). Also, SIV is distinct
from simian T-cell lymphotropic virus type I (STLY-I) which
shares extensive genomic sequences with human T-lymphotropic
virus type I and is associated with T-cell lymphomas in nonhuman
primates (12).

SIV can be isolated from a variety of tissues and body
fluids-including blood, plasma, cerebrospinal fluid, and
parenchyma tissues-of infected nonhuman' primates. Limited data
exist concerning the presence or concentration of virus in semen,
cervical secretions, saliva, urine, breast milk, and amniotic
fluids of experimentally or naturally infected nonhuman primates.
However, the virus apparently is rarely isolated from semen,
urine, and saliva despite repeated attempts at isolation (M.
Daniel, N. Lerche, personal communication). There is no evidence
to indicate that SIV is transmitted by the respiratory route (N.
Lerche, H. McClure, M. Daniel, personal communication).
The cell tropism of SIV in culture depends partially on the
strain of virus propagated and conditions of cell culture.
Strains of SIV have been successfully cultured in human
lymphocyte cell lines (e.g., HuT 78, HT, CEMx174) and in primary
human and nonhuman primate peripheral blood leukocyte cultures
(13). SIV appears to be primarily tropic for CD4 (T4)-positive
leukocytes and has not been successfully propagated in
B-lymphocyte cell lines (e.g., Raji). SIV antigen has been
demonstrated by immunohistochemical methods in lymph node sinus
histiocytes, macrophages, and giant cells (14) as well as in
macrophage-derived cells in brain tissue from diseased monkeys
(8).

Limited data exist concerning the reactivation of Herpesvirus
simiae (B virus) or other latent infectious agents in SIV
infected macaque monkeys. However, all macaque monkeys not proven
to be free of B virus infection, regardless of SIV infection
status, should be regarded as infected with B virus and handled
according to published guidelines (15). The routine screening of
macaques for evidence of B virus infection or SIV infection is
not recommended. However, in situations in which studies may
cause immunosuppression (e.g., during experimental SIV
infections), the investigator may elect to determine the
infection status of the animals because a virus shedding may be
enhanced in infected animals.

EVALUATING THE RISK OF SIV TRANSMISSlON TO HUMANS

The risk, if any, of human infection with SIV has not been
defined. However, since SIV shares many characteristics with HIV,
many of the same biosafety precautions are 700 indicated. No
serologic or virolcgic evidence of infection in humans exists;
specific precautions in handling SIV are based on recommendations
developed for HIV and other lentiviruses. No licensed tests exist
for serologic evaluation of humans exposed to SIV. The absence of
licensed tests complicates medical surveillance and
investigations of the virus infection following exposure to SIV.
In addition, the antigenic cross-reactivity between SIV and HIV
may complicate testing of exposed humans. However, standardized
serologic procedures that test for SIV antibody are used in
laboratories performing research with the virus. Recently, a
protein unique to SIV and HIV-2 (product of gene vpx) was used as
antigen in a serologic test that may allow easier distinction
between HIV-I and SIV antibodies (16). Furthermore, gene
amplification (i.e., polymerase chain reaction) may allow
differentiation of specific virus gene sequences directly from
specimens obtained from exposed persons. Based on these events,
development of specific and sensitive tests is under way.

GUIDELINES TO PREVENT SIV INFECTION

IN LABORATORY WORKERS AND ANIMAL HANDLERS

Exposure Concerns. In the laboratory, SIV must be presumed to be
present in all SIV cultures, in all materials derived from such
cultures, in all specimens from SIV antibody-positive nonhuman
primates, and in/on all equipment and devices coming in contact
with these materials. In this setting, the skin (especially when
scratches, cuts, abrasions, dermatitis, or other lesions are
present) and mucous membranes of the eye, nose, and mouth should
be considered as potential pathways for virus entry; contact of
these sites with SIV-containing materials should be considered an
exposure to SIV.

Biosafery Levels. Biosafety level (BSL) 2 standards and special
practices, containment equipment, and facilities, as described in
the CDC/NIH publication Biosafery in Microbiological and
Biomedical Laboratories (17), are recommended for activities
involving all clinical specimens, body fluids, and tissues from
SlY-infected primates, In laboratories maintaining BSL 2,
personnel must have documented specific training in handling
primate retroviruses, and the laboratory must have limited and
properly secured access and written standard operating procedures
for techniques in which SlY is used. Procedures involving
cultures of SlY should be conducted in biological safety cabinets
or other physical containment equipment.

Inoculation Precautions. In the research laboratory, inoculation
of SIV-containing material represents an important potential
route of exposure to SIV in humans. The use of syringes, needles,
glass, and other sharp objects should be avoided, but when their
use is essential, needles and disposable cutting instruments
should be discarded after use into a lidded puncture-resistant
container located in the work area. Needles should not be
resheathed, bent, broken, removed, or otherwise manipulated by
hand.

Gloves. Latex or vinyl gloves should be worn by all personnel
engaged in activities that may involve direct skin contact with
infectious specimens, cultures, or tissues. Gloves should not be
washed or disinfected for reuse; reuse of such gloves may cause
"wicking" (i.e., enhanced penetration of liquids through
undetected holes in the glove) or deterioration of the gloves.
When gloves have become visibly contaminated, they should be
carefully removed and, after the hands are washed, replaced with
a fresh pair of gloves. Handwashing with soap and water
immediately after infectious materials are handled and work is
completed, even when gloves have been worn, should be routine
practice.

Clothing. Laboratory coats, gowns, or uniforms should be worn by
laboratory workers when engaged in any work involving SlY or
materials known or suspected to contain SIV. Clothing that
becomes contaminated with SIV or SIV-containing materials should
be decontaminated before being laundered or discarded. Clothing
can be decontaminated by extensive soaking of the garment with
chemical disinfectants (e.g., 1 to 10 dilution of household
beach).

Aerosol Control. Although aerosol transmission of SIV has not
been demonstrated, the generation of aerosols, droplets,
splashes, and spills should be avoided. A biological safety
cabinet should be used for all procedures that might generate
aerosols or droplets and for all infected cell culture
manipulations. When centrifuging infected materials, centrifuge
containers with safety caps that are designed to contain aerosols
(in the event of spillage) should be used. When cell sorters are
used, plastic shielding or other containment devices should be
used to reduce exposure to infectious droplets.

Contaminated Virus Preparations. During the propagation of SIV in
the research laboratory, manipulation of concentrated virus
preparations or conduct of procedures that may produce aerosols
or droplets should be performed in a BSL 2 facility, with
additional practices and containment equipment recommended for
BSL 3 (17). These practices should include wearing closed-front
surgical-type gowns, masks and protective eyewear or face
shields, and latex or vinyl gloves that extend to cover the wrist
and sleeves of the surgical gown. Activities involving
large-volume production or manipulation of highly concentrated
SIV should be conducted in a BSL 3 facility, using only BSL 3
practices and equipment. All discarded cultures and laboratory
supplies used in experimental manipulations of cultures should be
autoclaved before disposal.

Decontamination. The susceptibility of SIV to chemical
disinfectants has not been defined. Work surfaces, however,
should be decontaminated daily with commercially available
chemical disinfectants such as sodium hypochlorite solution 10%
(1 to 10 dilution of household beach), ethanol 70%-85%, or
ethanol-iodine complex 2%. These effectively inactivate HIV-I
(18,19). Prompt decontamination of spills (immediate absorption
and control of the spill and soaking of the contaminated area
with chemical disinfectant) should be standard practice. Gloves
should be worn when cleaning up such spills. The use of
plastic-backed absorbent padding to control spillage during
manipulation of cultures or other SIV-containing fluids should be
encouraged.

Handling SIV-Infected Nonhuman Prlmates. Nonhuman primates
experimentally infected with SlY may have other primary, as well
as opportunistic, pathogens in their body fluids and tissues.
Thus, laboratory workers and animal handlers should follow
accepted BSL 2 practices at all times to prevent inadvertent
exposure to agents that may be present in clinical specimens or
body fluids. All macaque monkeys not known to be free of
Herpesvirus simiae (B virus) should be regarded as infected and
handled according to published guidelines (15).

Personnel Training. Primary investigators, other scientific
personnel and other persons who handle nonhuman primates used in
SIV research should be trained in proper methods of animal
restraint and use of protective clothing. Animal handlers should
be familiar with various drugs routinely used for providing
chemical restraint and with proper procedures for administering
medications. All persons engaged in research involving nonhuman
primates should be specifically trained in the natural history of
SIV infection. Particular attention should be given to the need
to wear protective clothing to prevent mucous membrane contact
with potentially infectious material, particularly animal blood
from an SIV-infected nonhuman primate. Caution should be
emphasized during venipuncture procedures or the administration
of injections to nonhuman primates involved in SIV research.
lntravenous injections of nonhuman primates should be done while
the animal is anesthetized and should be administered through a
plastic or teflon catheter with syringes fitted with interlocking
connectors.

Medical Surveillance. A licensed test specific for SIV antibody
is not yet available. Standardized serologic procedures to
identify SIV antibody are used in laboratories performing
research with the virus. A medical surveillance program should be
in place in all laboratories that test specimens, conduct
research, or produce reagents involving SIV. The nature and scope
of the surveillance program will vary by institutional policy and
applicable local, state, and federal regulations (20).
Laboratories performing research with SIV should initiate a
program to store serum from laboratory workers. Serum specimens
should be collected at 6-month intervals and stored. Routine
testing of the serum is optional but, if performed, should be
done using standardized serologic procedures in qualified
laboratories. Human Exposure to SIV, if a laboratory worker has a
parenteral, skin, or mucous membrane exposure to blood, body
fluids, or virus culture material from nonhuman primates, the
source material should be identified and, if possible, tested for
the presence of SlY. All wounds incurred from SIV-infected
nonhuman primates or from SIV-contaminated instruments should be
cleansed with soap and water. Such incidents should be reported
to the animal-care supervisor and/or laboratory supervisor and
recorded in an accident report log. If the source material is
positive for SIV antibody, virus, or antigen or unavailable for
examination, the worker should be counseled regarding the risk of
infection and evaluated medically. The worker should be advised
to report and to seek medical evaluation for any acute febrile
illness that occurs within 12 weeks after the exposure. Medical
evaluation should include examination for serum antibody against
SlY. Seronegative workers should be retested 6 weeks after the
exposure and periodically thereafter (e.g., 12 weeks and 6 months
after exposure). All institutions should establish written
policies regarding the management of laboratory exposure to SIV;
such policies should deal with confidentiality, counseling, and
other related issues. The lack of data concerning the potential
transmission of SIV between humans does not allow for specific
recommendations concerning behavior changes in a person
confirmed seropositive for SIV. However, an HIV-seropositive
person should not donate blood.

Postexposure Treatment. No effective prophylactic treatment for
SIV exists; research is needed in animals concerning postexposure
prophylaxis (e.g., immune globulin, antiviral therapy). Data from
such research may be useful in future exposures of humans to SIV.

US Department of Labor, US Department of Department of Health
and Human Services. Joint advisory notice: HBV/HIV. Federal
Register 1987;52(21O):41818-24.

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